It is reported, for example in U.S. Pat. No. 6,207,229, that II–VI semiconductor nanocrystals may be synthesized in a coordinating solvent, trialkyl phosphine/trialkyl phosphine oxide. The semiconductor nanocrystals are known to have optical characteristics that are different from those of bulk semiconductor. For example, the semiconductor nanocrystals are capable of coloring and emitting light of various wavelengths depending on their size, have a broad absorption range, and are excited to emit light by excitation light of a single wavelength. The fluorescence spectrum of the semiconductor nanocrystals is narrow and highly symmetric. Further, the semiconductor nanocrystals, compared to organic dyes, have superior durability and anti-fading property. As such, the semiconductor nanocrystals have recently been studied intensively for applications not only in optics and electronics such as display elements and recording materials, but also in fluorescent markers and biological diagnosis.
Quantum dots, which are semiconductor nanocrystals, are water-insoluble per se. For application in biological diagnosis, quantum dots thus have to be formed into a stable dispersion in water by changing/modifying their crystal surface. For solubilization of quantum dots in water, there are reported methods of bonding mercaptoethanol or thioglycerol, or low molecular thiol compounds such as mercaptoundecanoic acid or lipoic acid, to the surface of semiconductor nanocrystals (e.g., Journal of Physical Chemistry B, 103, 3065 (1999) and U.S. Pat. No. 6,319,426).
However, such water solubilizers have non-specific adsorption, which cannot be inhibited sufficiently for application in biological diagnosis. This may cause problems in highly sensitive detection of only the objective trace substance.
On the other hand, a report is made on the use of polyacrylic acid partially modified with octylamine for dispersing CdSe semiconductor nanocrystals having a ZnS shell in water (e.g., Nature Biotechnology, Online Version, 2(2002)). However, this method requires three steps for solubilization of semiconductor nanocrystals in water, and is thus complicated.
There is also a publication that discloses a concept of semiconductor nanocrystals as a material for biological diagnosis to which an affinity molecule is bonded via a linking agent (e.g., U.S. Pat. No. 5,990,479). However, this publication does not pay attention to inhibition of non-specific adsorption of the linking agent. Still less, no example is disclosed wherein the affinity molecule is actually bonded to semiconductor nanocrystals, but mere preparation of semiconductor nanocrystals is disclosed.
There is also proposed to solubilize semiconductor nanocrystals in water, such as those of CdSe having a ZnS shell, by bonding polyalkylene glycol having a thiol group at one end to the nanocrystals, for preparing a material for biological diagnosis (e.g., JP-2002-121549-A). However, this publication merely discloses examples wherein a derivative of short-chain trialkylene glycol is used as the polyalkylene glycol, and no example with long-chain polyalkylene glycol is disclosed. Such semiconductor nanocrystals having a trialkylene glycol derivative bonded thereto have problems in that, for example, when used as a material for biological diagnosis, the nanocrystals cannot form a stable bond with organic molecules having specific affinity to a particular substance, do not have sufficiently inhibited non-specific adsorption, and cannot be formed into a stable dispersion under physiological conditions.
Further, it is known that, when a low molecular thiol compound, such as a short-chain trialkylene glycol derivative, is used for solubilizing semiconductor nanocrystals in water, fluorescence intensity of the nanocrystals is remarkably lowered compared to the intensity in an organic solvent (e.g., Journal of Colloids and Surfaces, 202, 145 (2002)).